# The Inorganic Nitrate and eXercise performance in Heart Failure (iNIX-HF): - a phase II clinical trial

> **NIH NIH R61** · WASHINGTON UNIVERSITY · 2022 · $803,813

## Abstract

ABSTRACT
Heart failure with reduced ejection fraction (HFrEF) affects ~3 million people in the U.S. and is a mortal and
morbid disease. HFrEF impairs a patient’s ability to exercise and perform activities of daily living. Although weak
cardiac pumping ability clearly contributes to chronic disability associated with HFrEF, abnormal skeletal muscle
function in patients with HFrEF is also a key debilitating factor. Skeletal muscle is therefore a vital target for
treatment of HFrEF. Dietary inorganic nitrate enhances aerobic exercise capacity and muscle power in patients
with HFrEF, as demonstrated in our preliminary studies. The overarching aim of the proposed clinical trial is to
determine whether inorganic nitrate in a once-a-day oral gelcap format, offers a new, safe, and effective
treatment for ameliorating the impaired exercise performance due to HFrEF.
 The Aim of the R61 component of this grant is to set up the infrastructure necessary for the phase II
clinical trial and to begin the trial. This includes compounding the inorganic nitrate (KNO3)/placebo capsules and
all safety testing, obtaining Institutional Review Board approval, ClinicalTrials.gov registration, REDCap
database development, Recruitment Enhancement Core (REC) engagement, Clinical Translational Research
Unit (CTRU) project approval, enrollment and assessment and dose administration of the first subjects.
 The Aims of the R33 component are to determine the effectiveness of acute (2 hours after a single dose)
and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle
power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction
<45%). We hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise
performance in HFrEF. To test this hypothesis, we will perform a randomized, double-blind, placebo-controlled,
parallel-arm design study. Patients with stable New York Heart Association class I-III HFrEF will undergo
screening and phenotyping before completing baseline peak muscle power and aerobic performance
measurements. On visit 2, subjects will receive a single dose (1 capsule) of their assigned treatment (10mmol
KNO3 or placebo) and will repeat the measurements of exercise performance after 2h. Subjects will then continue
with their assigned treatment (KNO3 or placebo, 1 capsule daily) for 6 weeks. On visit 3, subjects will repeat the
tests of exercise performance. The primary endpoints are maximum quadriceps muscle power, measured using
an isokinetic dynamometer, and aerobic exercise performance, based on V̇O2peak. Max exercise time and max
muscle velocity, tolerability and safety of KNO3 vs. placebo treatment and their effects on hemodynamics, plasma
nitrate, plasma nitrite, breath nitric oxide (NO), and heart failure symptoms (using well-validated questionnaires)
will also be quantified in this phase II, single-center clinical trial. The potential impact ...

## Key facts

- **NIH application ID:** 10449833
- **Project number:** 1R61HL155858-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** ANDREW R COGGAN
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $803,813
- **Award type:** 1
- **Project period:** 2022-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449833

## Citation

> US National Institutes of Health, RePORTER application 10449833, The Inorganic Nitrate and eXercise performance in Heart Failure (iNIX-HF): - a phase II clinical trial (1R61HL155858-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10449833. Licensed CC0.

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